A phase II study of osimertinib in combination with platinum plus pemetrexed in patients with EGFR-mutated, advanced non–small cell lung cancer: The OPAL study (NEJ032C/LOGIK1801).
Authors: Atsushi Nakamura, Ryota Saito, Ryo Ko, Koichi Azuma, Ryo Morita, Makoto Maemondo, Satoshi Oizumi, Kazuhisa Takahashi, Hiroshi Kagamu, Takeshi Isobe, Masahiro Seike, Toshiaki Kikuchi, Isamu Okamoto, Satoshi Morita, Hajime Asahina, Kentaro Tanaka, Kenji Sugio, Kunihiko Kobayashi
Journal: Journal of Clinical Oncology (2022)

9097 Background: Osimertinib (OSI), a third-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI), is now a standard treatment for previously untreated EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC). In the two randomized phase 3 studies, progression-free survival (PFS) and overall survival were statistically significant and clinically longer with gefitinib and platinum-based chemotherapy compared with gefitinib monotherapy. Based on these data, we have planned this phase 2 study to evaluate the safety and efficacy of OSI combined with platinum-based chemotherapy. Patients and Methods: This multicenter phase 2 study enrolled patients (pts) with clinical stage IIIB, IIIC, IVA, IVB or postoperative recurrent, previously untreated EGFRm NSCLC. Pts received oral OSI 80mg once daily (QD), with either cisplatin 75mg/m2 (arm A) or carboplatin [area under the curve (AUC) = 5, arm B], plus pemetrexed (PEM) 500 mg/ m2 every 3 weeks (Q3W) for four cycles. In both arms, maintenance was OSI 80mg QD with PEM 500 mg/ m2 Q3W until disease progression or discontinuation. The co-primary endpoints were the safety and the objective response rate (ORR), and the secondary endpoints included the complete response rate (CRR), disease control rate (DCR), and PFS. Results: From July 2019 to February 2020, 67 pts (34 pts in Arm A; 33 pts in arm B) were enrolled: median (range) age 67 (26-75) years; 43 (64.2%) female; 46 (68.7%) ECOG PS 0; 66 (98.5%) adenocarcinoma; 31 (46.3%) EGFR exon19 deletion, 35 (52.2) L858R, and 1 (1.5%) both. One pt did not comply with the eligibility criteria and was excluded from the efficacy analysis. At data cut off (August 31, 2021), 27 (40.3%) pts [15 (44.1%) in arm A and 12 (36.4%) in arm B] had discontinued the protocol treatment, including 9 (13.4%) pts [5 (14.7%) in arm A and 4 (12.1%) in arm B] due to the adverse event (AE). The rate of grade (G) ≥ 3 AEs were 91.0% (88.2% in arm A and 93.9% in arm B). For the safety, neutropenia, anemia and thromobocytopenia were numerically higher in arm B and the rates of G ≥ 3 were 29.4%/60.6%, 14.7%/27.3% and 0.0%/42.4% in arm A/B, respectively. G ≥ 3 QTc interval prolonged and G ≥ 2 anorexia were observed in 14.7%/21.2% and 26.5%/24.2%, respectively. For the efficacy, the ORR was 90.9% [95% confidence interval (CI); 84.0-97.8%]. The CRR/DCR were 3.0%/97.0% (95% CI; 0.0-7.2%/92.8%-100.0%), respectively. At a median follow-up time of 21.4 months (range, 18.2-25.7), median PFS was not reached in both A and B, with an estimated 12-/24-months PFS rate of 90.4%/70.0%. Conclusions: OSI combined with platinum-based chemotherapy for previously untreated EGFRm advanced NSCLC showed the excellent efficacy with tolerable toxicity. This combination treatment is highly promising and should be validated in the phase 3 study. Clinical trial information: jRCTs031180226.